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Pd/C-mediated depropargylation of propargyl ethers/amines in water D. Rambabu a , S. Bhavani b , Nalivela Kumara Swamy c , M. V. Basaveswara Rao d,, Manojit Pal a,a Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India b Department of Chemistry, K. L. University, Vaddeswaram, Guntur 522 502, Andhra Pradesh, India c Organic Chemistry Institute, University of Heidelberg, Im Neuenheimer Feld 271, 69120 Heidelberg, Germany d Department of Chemistry, Krishna University, Machilipatnam 521001, Andhra Pradesh, India article info Article history: Received 18 November 2012 Revised 19 December 2012 Accepted 22 December 2012 Available online 2 January 2013 Keywords: Propargyl ether/amine Deprotection Pd/C Water abstract Propargyl ethers and amines are effectively depropargylated to the parent alcohols or amines via a CO/CN bond cleavage catalyzed by 10% Pd/C in water. This simple, facile, and inexpensive methodol- ogy could be utilized for the selective removal of propargyl groups from a variety of aryl ethers and amines. Ó 2012 Elsevier Ltd. All rights reserved. Protection/deprotection of organic functional groups is of enor- mous importance in organic synthesis 1 especially in the synthesis of complex natural products. Thus development of elegant method- ologies attaining high functional group compatibility and selectiv- ity is desirable for this purpose. Among the various protecting groups propargyl group is attractive due to the presence of two orthogonal p-bonds, which perhaps help in its facile cleavage in the presence of transition metal complexes. 2 A number of reports are available in the literature for the cleavage of the carbon oxy- gen 3 /carbon nitrogen 4 bond in a variety of compounds such as allyl, vinyl, and benzyl ethers/amines. Although the cleavage of C–O bonds in allylethers/esters has been thoroughly investigated, only a few examples are known dealing with the cleavage of the C–X (X = O, N) bond in propargyl ethers/esters or amines. These include the use of low valent titanium, 5 hydrogenolysis of propargyl esters with formic acid or formates, 6 nickel-catalyzed electro reductive cleavage of propargyl compounds, 7 palladium-catalyzed reductive cleavage of propargyl esters mediated by Bu 3 SnH or by SmI 2 , 8 cleav- age of propargyl ethers or propargyl oxycarbonyl protected amines with tetrathiomolybdate, 9 and oxidative cleavage of 1-naphthyl propargyl ether or allenyl ether generated by the treatment with KO t Bu followed by catalytic OsO 4 and N-methyl morpholine N- oxide. 10 Allyl and propargyl ethers were effectively deallylated or depropargylated to the parent alcohols via a CO bond cleavage catalyzed by a low-valent titanium reagent (LVT). 11 The combina- tion of SmI 2 –amine–water has also been explored as a catalyst system for the removal of propargyl groups. 12 While many of these methods are useful most of them however required either the use of multiple reagents or prior preparation of the actual reagent. 5,8,9 Moreover, a few of them were found to be incompatible with sev- eral functional groups especially halogens 7 where dehalogenation was observed frequently. Earlier, we have developed a copper-free palladium-mediated cleavage of O/N propargyl bonds in aqueous media affording a mild and convenient method for the deprotection of phenols and anilines. 13 While this reaction was found to be effec- tive the methodology, however, involved the use of relatively expensive palladium catalyst, that is, (PPh 3 ) 2 PdCl 2 and an organic co-solvent, for example, DMF along with water. Recently, the use of Pd/C has been explored as efficient and effective catalyst for var- ious C–C bonds forming reaction either in pure water or other or- ganic solvent. 14 The catalyst Pd/C is stable and easy to handle as well as separable from the product. Moreover, the catalyst can be recycled. This prompted us to explore the use of Pd/C as an alterna- tive catalyst in the cleavage of O/N-propargyl bonds. We chose water as a medium in the present transformation as the water based reactions are inherently safer and inexpensive. Herein we re- port our preliminary results on Pd/C-mediated depropargylation of propargyl ethers/amines (1) in water in the presence of 2-ethanol- amine (Scheme 1). In our earlier study Et 3 N was used as a base/ligand in the ab- sence of which the reaction did not proceed. 13 However, being vol- atile the nitrogen containing agent Et 3 N is likely to cause environmental hazard especially in a large scale preparation. We envisioned that 2-ethanolamine in place of Et 3 N could facilitate the depropargylation reaction in water because of its better 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2012.12.093 Corresponding authors. Tel.: +91 40 6657 1500; fax: +91 40 6657 1581. E-mail address: [email protected] (M. Pal). Tetrahedron Letters 54 (2013) 1169–1173 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet

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Page 1: Pd/C-mediated depropargylation of propargyl ethers/amines in water

Tetrahedron Letters 54 (2013) 1169–1173

Contents lists available at SciVerse ScienceDirect

Tetrahedron Letters

journal homepage: www.elsevier .com/ locate/ tet le t

Pd/C-mediated depropargylation of propargyl ethers/amines in water

D. Rambabu a, S. Bhavani b, Nalivela Kumara Swamy c, M. V. Basaveswara Rao d,⇑, Manojit Pal a,⇑a Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, Indiab Department of Chemistry, K. L. University, Vaddeswaram, Guntur 522 502, Andhra Pradesh, Indiac Organic Chemistry Institute, University of Heidelberg, Im Neuenheimer Feld 271, 69120 Heidelberg, Germanyd Department of Chemistry, Krishna University, Machilipatnam 521001, Andhra Pradesh, India

a r t i c l e i n f o a b s t r a c t

Article history:Received 18 November 2012Revised 19 December 2012Accepted 22 December 2012Available online 2 January 2013

Keywords:Propargyl ether/amineDeprotectionPd/CWater

0040-4039/$ - see front matter � 2012 Elsevier Ltd. Ahttp://dx.doi.org/10.1016/j.tetlet.2012.12.093

⇑ Corresponding authors. Tel.: +91 40 6657 1500; fE-mail address: [email protected] (M. Pa

Propargyl ethers and amines are effectively depropargylated to the parent alcohols or amines via aC�O/C�N bond cleavage catalyzed by 10% Pd/C in water. This simple, facile, and inexpensive methodol-ogy could be utilized for the selective removal of propargyl groups from a variety of aryl ethers andamines.

� 2012 Elsevier Ltd. All rights reserved.

Protection/deprotection of organic functional groups is of enor-mous importance in organic synthesis1 especially in the synthesisof complex natural products. Thus development of elegant method-ologies attaining high functional group compatibility and selectiv-ity is desirable for this purpose. Among the various protectinggroups propargyl group is attractive due to the presence of twoorthogonal p-bonds, which perhaps help in its facile cleavage inthe presence of transition metal complexes.2 A number of reportsare available in the literature for the cleavage of the carbon oxy-gen3/carbon nitrogen4 bond in a variety of compounds such as allyl,vinyl, and benzyl ethers/amines. Although the cleavage of C–Obonds in allylethers/esters has been thoroughly investigated, onlya few examples are known dealing with the cleavage of the C–X(X = O, N) bond in propargyl ethers/esters or amines. These includethe use of low valent titanium,5 hydrogenolysis of propargyl esterswith formic acid or formates,6 nickel-catalyzed electro reductivecleavage of propargyl compounds,7 palladium-catalyzed reductivecleavage of propargyl esters mediated by Bu3SnH or by SmI2,8 cleav-age of propargyl ethers or propargyl oxycarbonyl protected amineswith tetrathiomolybdate,9 and oxidative cleavage of 1-naphthylpropargyl ether or allenyl ether generated by the treatment withKOtBu followed by catalytic OsO4 and N-methyl morpholine N-oxide.10 Allyl and propargyl ethers were effectively deallylated ordepropargylated to the parent alcohols via a C�O bond cleavagecatalyzed by a low-valent titanium reagent (LVT).11 The combina-tion of SmI2–amine–water has also been explored as a catalyst

ll rights reserved.

ax: +91 40 6657 1581.l).

system for the removal of propargyl groups.12 While many of thesemethods are useful most of them however required either the use ofmultiple reagents or prior preparation of the actual reagent.5,8,9

Moreover, a few of them were found to be incompatible with sev-eral functional groups especially halogens7 where dehalogenationwas observed frequently. Earlier, we have developed a copper-freepalladium-mediated cleavage of O/N propargyl bonds in aqueousmedia affording a mild and convenient method for the deprotectionof phenols and anilines.13 While this reaction was found to be effec-tive the methodology, however, involved the use of relativelyexpensive palladium catalyst, that is, (PPh3)2PdCl2 and an organicco-solvent, for example, DMF along with water. Recently, the useof Pd/C has been explored as efficient and effective catalyst for var-ious C–C bonds forming reaction either in pure water or other or-ganic solvent.14 The catalyst Pd/C is stable and easy to handle aswell as separable from the product. Moreover, the catalyst can berecycled. This prompted us to explore the use of Pd/C as an alterna-tive catalyst in the cleavage of O/N-propargyl bonds. We chosewater as a medium in the present transformation as the waterbased reactions are inherently safer and inexpensive. Herein we re-port our preliminary results on Pd/C-mediated depropargylation ofpropargyl ethers/amines (1) in water in the presence of 2-ethanol-amine (Scheme 1).

In our earlier study Et3N was used as a base/ligand in the ab-sence of which the reaction did not proceed.13 However, being vol-atile the nitrogen containing agent Et3N is likely to causeenvironmental hazard especially in a large scale preparation. Weenvisioned that 2-ethanolamine in place of Et3N could facilitatethe depropargylation reaction in water because of its better

Page 2: Pd/C-mediated depropargylation of propargyl ethers/amines in water

H2O, 80 °C5-6 h, N2

Ar XAr XH

1 2

10% Pd/C2-Ethanolamine

Scheme 1. The deprotection of propargyl ethers and amines.

Table 1Effect of reaction conditions on Pd/C-mediated depropargylation of 1-nitro-4-(prop-2-ynyloxy)benzene (1a)a

O2N

O

H2O, 80 ºC5 h, N2

10% Pd/C2-Ethanolamine

O2N

OH

1a 2a

Entry Mol % of Pd/Ccatalyst used

Equivalent of2-ethanolamine used

Yieldb (%)

1 5.0 3.0 852 4.0 3.0 873 3.0 3.0 524 4.0 2.0 465 4.0 0 06 4.0 3.0 0c

a All the reactions were carried out using 1a (1.1 mmol), 2-ethanolamine, and10% Pd/C in water (4 mL) at 80 �C for 5 h under nitrogen.

b Isolated yield.c The reaction was performed in the presence of Hg.

Table 2Pd/C-mediated deprotection of aryl propargyl ethers/amines in watera

Entry Propargyl derivatives (1)

1 O2N

O

1a

2 H3CO

O

1b

3 NC

O

1c

4 Br

O

1d

5O

O

1e

6 O

O

1f

7 O

O

1g

1170 D. Rambabu et al. / Tetrahedron Letters 54 (2013) 1169–1173

miscibility with water. Moreover, due to its lower volatility (there-by avoiding internal pressure development as well as ensuring itsmaximum recovery) in comparison to Et3N, 2-ethanolamine ap-peared to be a better choice in the present reaction. Thus, whenpropargyl ethers/amines (1) were treated with 10% Pd/C (205699Aldrich) in water in the presence of 2-ethanolamine at 80 �C for5–6 h the corresponding phenols/amines (2) were isolated in goodyields.15 A preliminary and focused optimization study using 1-ni-tro-4-(prop-2-ynyloxy)benzene (1a) as substrate indicated that�4 mol % of 10% Pd/C was necessary for the best result (Table 1, en-tries 1–3). A decrease in catalyst quantity from 4 to 3 mol % re-duced the product yield significantly (Table 1, entry 3). Similarly,the quantity of 2-ethanolamine (i.e., 3 equiv) used was found tobe vital as decrease in its amount lowered the product yield (Table1, entry 2 vs 4). Perhaps, in addition to its participation in the gen-eration of active and water soluble catalytic species for C–X bondcleavage 2-ethanolamine appeared to play a key role in solubilizingthe substrates in pure water. The reaction did not proceed in theabsence of 2-ethanolamine (Table 1, entry 5). The reaction alsodid not proceed when performed in the presence of mercury (Hg)(Table 1, entry 6) perhaps due to the accumulation of Hg on thecharcoal surface thereby alloying with Pd through dp–dp bonding(the catalyst poisoning).16

Having established the optimized reaction conditions we thenexamined the generality and scope of this Pd/C-mediated deprop-argylation reaction. The results of this study are summarized in

Productsb (2) Yieldc (%)

O2N

OH

2a

87

H3CO

OH

2b

78

NC

OH

2c

87

Br

OH

2d

72

O

OH

2e

74

O

OH

2f

65

O

OH

2g

82

Page 3: Pd/C-mediated depropargylation of propargyl ethers/amines in water

Table 2 (continued)

Entry Propargyl derivatives (1) Productsb (2) Yieldc (%)

8O

O

1h

O

OH

2h

52

9

O

1i

OH

2i

73

10

O

1j 2j

OH

69

11

HN

O

1k

HN

HO

2k

77

12N

O

1l

N

HO

2l

64

13N

O

O

1m

N

HO

O

2m

62

14

N

O

CH3

1n

N

HO

CH3

2n

57

15 H3CO

HN

1o

H3CO

NH2

2o

82

16 H3CO

HNCl

1p

H3CO

NH2Cl

2p

85

17

HNF

1q

NH2F

2q

76

18F3CO

HN

1r

F3CO

NH2

2r

61

(continued on next page)

D. Rambabu et al. / Tetrahedron Letters 54 (2013) 1169–1173 1171

Page 4: Pd/C-mediated depropargylation of propargyl ethers/amines in water

Table 2 (continued)

Entry Propargyl derivatives (1) Productsb (2) Yieldc (%)

19

HN

F

1s

NH2

F

2s

55

a All the reactions were carried out using the compound 1 (1.1 mmol), 2-ethanolamine (3.3 mmol), and 10% Pd/C (0.045 mmol) in water (4 mL) at 80 �C for 5–6 h undernitrogen.

b Identified by 1HNMR, IR, mass.c Isolated yield.

Pd/C

Pdleaching Pd in

solution complex insolution

Pd(0)

Precipitation ofPd on C at the endof catalytic cycle

Generation of actualcatalytic species

The catalyticcycle

Ar X1

C C CH

H H

[Pd]

E-1

OH

NH2

OH

NH2Pd(0)

H2O

ArX

C C CH

H H

[Pd] ArXH

OH

C C CH

H H

[Pd] ArXH

OH

H2O

OOH+ArXH

2E-2

Scheme 2. Proposed mechanism for the Pd/C catalyzed depropargylation reaction.

1172 D. Rambabu et al. / Tetrahedron Letters 54 (2013) 1169–1173

Table 2. A wide variety of arylpropargyl ethers and amines werecleaved to the corresponding phenols and amines. Various substit-uents on the phenyl ring of the starting ether or amine (1) werewell tolerated under the condition of the reaction employed. Ethersafforded good yields of products irrespective of the presence of anelectron withdrawing group such as nitro and cyano (Table 2, en-tries 1 and 3), or electron donating group, for example, methoxyand bromo (Table 2, entries 2 and 4) on the phenyl ring. A remark-able selectivity toward O-depropargylation was observed when theO-allyl (Table 2, entries 5 and 6) or O-benzyl moiety (Table 2,entries 7 and 8) was present in the substrate in addition to theO-propargyl group. Ethers containing poly nuclear aromatic ringsuch as naphthyl (Table 2, entries 9 and 10) or heteroaryl groupsuch as indole (Table 2, entries 11–14) were depropargylated un-der the conditions employed. A number of arylpropargyl aminescontaining substituents like OMe, Cl, F, or OCF3 were depropargy-lated (Table 2, entries 16–19) using the present method. Overall,the chloro group was found to be well tolerated in this Pd/C-med-iated reaction, as no dechlorinated products were detected in thesecases (Table 2, entries 4 and 16). Also, reducible functional groups,for example, nitro present in the substrate remained unaffected(Table 2, entry 1). While the methodology worked for a range ofsubstrates it has shown some limitations. For example, an attemptto deprotect 1,4-bis(prop-2-ynyloxy)benzene afforded a complexmixture of unidentified products. Similarly, the N-deprotection of1-(prop-2-ynyl)-1H-indole using the present methodology re-mained unsuccessful. Also yields of the depropargylated productswere not particularly high in certain cases (Table 2, entries 8, 14,19 etc.).

We have shown that a variety of aryl propargyl ethers andamines (1) can be deprotected in a regio-selective manner using10% Pd/C as a catalyst in water without affecting the other func-tional groups. A plausible mechanism for this Pd/C-mediated

depropargylation is shown in Scheme 2. The C–X bond cleavageproceeds via generation of an active Pd(0) species in situ whichreacts with propargylether or amine leading to the formation ofan allenylpalladium intermediate E-1. The active Pd(0) species isgenerated from the minor portion of the bound palladium (Pd/C) via a Pd leaching process into the solution.14 The leaching ofPd in a Pd/C-mediated coupling reaction has been investigatedand confirmed earlier.17 The leached Pd then becomes an activespecies by interacting with water miscible 2-ethanolamine li-gands. Thus, a dissolved Pd(0)/2-ethanolamine complex (whichexpected to have enhanced solubility in water) is the active spe-cies that actually catalyzes the depropargylation reaction in solu-tion. The catalytic cycle therefore works in solution rather than onthe surface and at the end of the reaction re-precipitation of Pdoccurs on the surface of the charcoal. Once generated, the allenyl-palladium species E-1 then undergoes nucleophilic attack on thecentral sp carbon by a water molecule followed by tautomeriza-tion to afford the a-Pd carbonyl intermediate E-2. Subsequenthydrolysis of E-2 released the desired phenol or aniline (2) withthe regeneration of Pd(0) to complete the catalytic cycle. The pro-posed mechanism was further supported by the detection ofhydroxyacetone (1-hydroxy-2-propanone) as a side product inthe reaction mixture.

In conclusion, we have described a facile and inexpensive Pd/C-mediated regioselective deprotection of aryl propargyl amines andethers in water. To the best of our knowledge this is the only exam-ple of cleavage of O/N-propargyl bonds catalyzed by Pd/C in water.The limitations and advantages of the methodology are discussed.Due to its operational simplicity, and functional group tolerabilitythe present methodology certainly has advantages and could be-come a useful alternative to the existing methods. The methodol-ogy therefore would find a wide usage in the protecting groupchemistry as well as organic synthesis.

Page 5: Pd/C-mediated depropargylation of propargyl ethers/amines in water

D. Rambabu et al. / Tetrahedron Letters 54 (2013) 1169–1173 1173

Acknowledgment

The authors thank the management of Dr. Reddy’s Institute ofLife Sciences for continuous support and encouragement.

References and notes

1. (a) Green, T. W.; Wuts, P. G. M. Protectie Groups in Organic Synthesis, 3rd ed.;John Wiley: New York, 1999. 67; (b) Guibe, F. Tetrahedron 1997, 53, 13509; (c)Guibe, F. Tetrahedron 1998, 54, 2967.

2. (a) Kandikere, R. P.; Naduthambi, D.; Chandrasekaran, S. Synlett 2002, 1762; (b)Nandi, B.; Das, K.; Kundu, N. G. Tetrahedron Lett. 2000, 41, 7259.

3. (a) Deelman, B. J.; Booij, M.; Meetsma, A.; Teuben, J. H.; Kooijman, H.; Spek, A. L.Organometallics 1995, 14, 2306; (b) Takaki, K.; Kusodo, T.; Uebori, S.; Makioka,Y.; Taniguchi, Y.; Fujiwara, Y. Tetrahedron Lett. 1995, 36, 1505; (c) Takaki, K.;Maruo, M.; Kamata, T.; Makioka, Y.; Fujiwara, Y. J. Org. Chem. 1996, 61, 8332;(d) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart, Germany, 1994, p. 61.;(e) Greene, T. W.; Wuts, P. G. M. Protectie Groups in Organic Synthesis, 2nd ed.;John Wiley: New York, 1991. 42; (f) Gigg, R. J. Chem. Soc., Perkin Trans. 1 1979,712; (g) Gigg, J.; Gigg, R. J. Chem. Soc. C 1966, 8286; (h) Corey, E. J.; Suggs, W. J. J.Org. Chem. 1973, 38, 3224.

4. (a) Talukdar, S.; Banerji, A. Synth. Commun. 1996, 1051, 26; (b) Talukdar, S.;Nayak, S. K.; Banerji, A. J. Org. Chem. 1998, 63, 4925.

5. (a) Kadam, S. M.; Nayak, S. K.; Banerji, A. Tetrahedron Lett. 1992, 33, 5129; (b)Nayak, S. K.; Kadam, S. M.; Banerji, A. Synlett 1993, 581; (c) Rele, S.; Talukdar,T.; Banerji, A. Tetrahedron Lett. 1999, 40, 767.

6. (a) Tsuji, J.; Mandai, T. Synthesis 1996, 1, 1; (b) Tsuji, J.; Mandai, T. Angew. Chem.,Int. Ed. Engl. 1995, 34, 2589.

7. Olivero, S.; Dunach, E. Tetrahedron Lett. 1997, 38, 6193.8. (a) Zhang, H. X.; Guibe, F.; Balavoine, G. Tetrahedron Lett. 1988, 29, 619; (b)

Inanaga, J.; Sugimoto, Y.; Hanamoto, T. Tetrahedron Lett. 1992, 33, 7035; (c)Aurrecoechea, J. M.; Anton, R. F. J. Org. Chem. 1994, 59, 702.

9. (a) Swamy, V. M.; Ilankumaran, P.; Chandrasekaran, S. Synlett 1997, 513; (b)Sinha, S.; Ilankumaran, P.; Chandrasekaran, S. Tetrahedron Lett. 1999, 40, 771.

10. (a) Crich, D.; Jayalath, P. Org. Lett. 2005, 7, 2277; (b) Crich, D.; Jayalath, P.;Hutton, T. K. J. Org. Chem. 2006, 71, 3064; (c) Crich, D.; Wu, B. Org. Lett. 2006, 8,4879.

11. Ohkubo, M.; Mochizuki, S.; Sano, T.; Kawaguchi, Y.; Okamoto, S. Org. Lett. 2007,9, 773.

12. (a) Dahlén, A.; Hilmersson, G. Tetrahedron Lett. 2002, 43, 7197; (b) Kim, M.;Knettle, B. W.; Dahlén, A.; Hilmersson, G.; Flowers, R. A. Tetrahedron 2003, 59,10397; (c) Dahlén, A.; Hilmersson, G. Tetrahedron Lett. 2003, 44, 2661; (d)Dahlén, A.; Hilmersson, G.; Knettle, B. W.; Flowers, R. A. J. Org. Chem. 2003, 68,4870; (e) Dahlén, A.; Nilsson, A.; Hilmersson, G. J. Org. Chem. 2006, 71, 1571; (f)Manabe, S.; Ueki, A.; Ito, Y. Tetrahedron Lett. 2008, 49, 5159.

13. Pal, M.; Parasuraman, K.; Yeleswarapu, K. R. Org. Lett. 2003, 5, 349.14. For a review, see: Pal, M. Synlett 2009, 2896.15. General procedure for the depropargylation reaction: To a mixture of aryl

propargyl ether/amine 1 (1.1 mmol) in water (4 mL) was added 2-ethanolamine (3.3 mmol) and 10% Pd/C (0.045 mmol). The mixture was thenstirred at 80 �C for 5–6 h under nitrogen. After completion of the reaction, themixture was diluted with water (10 mL), acidified with cold 2N HCl, andextracted with ethyl acetate (2 � 40 mL). The organic layers were collected,combined, washed with cold water (2 � 50 mL), dried over anhydrous Na2SO4,filtered, and concentrated under low vacuum. The residue was purified bycolumn chromatography using hexane/EtOAc as eluant to afford the desiredcompound 2.(b) Notably, 90% conversion was also observed when depropargylation of 1-nitro-4-(prop-2-ynyloxy)benzene (1a) was performed using 4 mol % of(PPh3)2PdCl2 in the presence of 2-ethanolamine in water at 80 �C for 5 h. Wethank one of the reviewer for pointing out this.

16. Dunleavy, J. K. Platinum Met. Rev. 2006, 50, 6. http://dx.doi.org/10.1595/147106706X128403.

17. (a) Chen, J.-S.; Vasiliev, A. N.; Panarello, A. P.; Khinast, J. G. Appl. Catal., A Gen.2007, 325, 76; (b) To gain further evidence 10% Pd/C (0.045 mmol) in water(4 mL) was treated with 2-ethanolamine (3.3 mmol) and the mixture wasstirred for 1 h. The mixture was then filtered to remove Pd/C and the filtratewas used for a new reaction by adding 1a without adding an additionalcatalyst. The mixture was then stirred at 80 �C for 5 h under nitrogen when 75%conversion was observed.